crossing96/oncoscreening huggingface dataset:
Holistic Assessment of Quality of Life Predicts Survival in Older Patients with Bladder Cancer.	OBJECTIVE: To determine if clustering methods can use a holistic assessment of health-related quality-of-life after bladder cancer diagnosis to predict survival outcomes independent of clinical characteristics. In the United States, an estimated 81,180 cases of bladder cancer will be diagnosed in 2022. We aim to help address the knowledge gap concerning the impact of patient functional status on outcomes. MATERIALS AND METHODS: This is a cross-sectional, retrospective cohort study of patients in the End Results-Medicare Health Outcomes Survey Registry. Age and 36-Item Short Form Survey (SF-36) responses were used as K-means inputs to identify homogenous clusters of older patients with bladder cancer. We analyzed the association between the identified clusters, patient and disease characteristics, and outcomes. We used Cox proportional hazard regression to compare overall survival. RESULTS: We identified 5 homogenous clusters that exhibited differences in patient characteristics and survival. There was no significant difference in cancer stage or surgery type among the clusters. The Cox proportional hazard regression demonstrated significant associations of cluster with gender, age, education, marital status, smoking status, type of surgery, and cancer stage on overall survival. Cluster independently predicted overall survival. CONCLUSION: Using unsupervised machine learning, we identified clusters of patients with bladder cancer who had similar mental and physical function scores. Cluster grouping suggests that patients' mental and physical function may not be based on disease or treatment. There are significant survival differences between all clusters, demonstrating that a holistic assessment of patient-reported health-related quality-of-life has the potential to predict survival and possible modifiable risk factors in older patients with bladder cancer.	bladder
Bacille Calmette Guerin (BCG) and prevention of types 1 and 2 diabetes: Results of two observational studies.	BACKGROUND: Diabetes is a common disease marked by high blood sugars. An earlier clinical trial in type 1 diabetic subjects (T1Ds) found that repeat BCG vaccinations succeeded in lowering HbA1c values over a multi-year course. Here we seek to determine whether BCG therapy for bladder cancer may improve blood sugar levels in patients with comorbid T1D and type 2 diabetes (T2D). We also investigate whether BCG exposure may reduce onset of T1D and T2D by examining country-by-country impact of BCG childhood vaccination policies in relation to disease incidence. METHODS AND FINDINGS: We first analyzed three large US patient datasets (Optum Labs data [N = 45 million], Massachusetts General Brigham [N = 6.5 million], and Quest Diagnostics [N = 263 million adults]), by sorting out subjects with documented T1D (N = 19) or T2D (N = 106) undergoing BCG therapy for bladder cancer, and then by retrospectively assessing BCG's subsequent year-by-year impact on blood sugar trends. Additionally, we performed an ecological analysis of global data to assess the country-by-country associations between mandatory neonatal BCG vaccination programs and T1D and T2D incidence. Multi-dose BCG therapy in adults with comorbid diabetes and bladder cancer was associated with multi-year and stable lowering of HbA1c in T1Ds, but not in T2Ds. The lack of a similar benefit in T2D may be due to concurrent administration of the diabetes drug metformin, which inhibits BCG's beneficial effect on glycolysis pathways. Countries with mandatory neonatal BCG vaccination policies had a lower incidence of T1D in two international databases and a lower incidence of T2D in one of the databases. CONCLUSIONS: The epidemiological evidence analyzed here suggests that BCG may play a role in the prevention of T1D. It does not support prevention of T2D, most likely because of interference by metformin. Our ecological analysis of global data suggests a role for neonatal BCG in the prevention of T1D and, to a lesser extent, T2D. Randomized clinical trials are needed to confirm these findings.	bladder
Fremantle protocol: Multicenter clinical outcomes for a pragmatic protocol for intravesical bacillus Calmette-Guerin.	OBJECTIVES: To examine the utility and efficacy of a multifaceted protocol for the administration of intravesical bacillus Calmette-Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC). SUBJECTS AND METHODS: A multicenter retrospective review was conducted among 83 patients undergoing Fremantle protocol intravesical BCG for NMIBC within 4 major hospitals in Western Australia between January 2016 and December 2018. The Fremantle protocol consists of weekly BCG instillations for 6 weeks during the induction phase, followed by monthly BCG instillations for 10 months during the maintenance phase with integrated clearance-to-proceed algorithms for urine MSU checks, flexible cystoscopies performed at 3 monthly intervals during maintenance BCG, and repeat GA cystoscopies with four quadrant bladder biopsies routinely obtained following the completion of induction and maintenance treatment. RESULTS: For patients undergoing Fremantle protocol BCG, 98.8% (82/83) and 75.9% (63/83) of patients completed their induction and maintenance courses of BCG, respectively. Induction BCG was delivered over a median duration of 35 days (range 34-84 days), and maintenance BCG was delivered over a median duration of 266 days (range 1-682 days). The tumor recurrence rate was 10.8% (9/83) at the time of post-induction biopsies, 2.4% (2/83) during maintenance treatment, 0% (0/60) at the time of post-maintenance biopsies, and 8.8% (5/57) after a median further follow-up of 16 months (range 0-51 months). CONCLUSION: The Fremantle protocol appears to be a safe and effective BCG regimen with several advantages over other BCG protocols, including high completion rates, low recurrence rates, and being highly pragmatic.	bladder
Efficacy and Safety of Mitomycin Gel (UGN-101) as an Adjuvant Therapy After Complete Endoscopic Management of Upper Tract Urothelial Carcinoma.	PURPOSE: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. RESULTS: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P = .28). CONCLUSIONS: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.	bladder
Health-related quality of life after curative treatment for muscle-invasive bladder cancer.	Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which the gold-standard treatment is radical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy. Bladder-sparing strategies such as trimodal therapy (TMT) have also emerged to improve health-related quality of life (HRQoL) of patients. However, an improved understanding of the effect of all these treatment modalities on HRQoL is essential to provide personalized patient care. Different combinations of generic, cancer-specific and bladder cancer-specific questionnaires can be used as instruments for HRQoL evaluation in patients with MIBC before and after curative treatments, which can largely affect multiple domains of HRQoL including general health as well as physical, functional, social and emotional well-being. However, diagnosis of MIBC per se is also likely to affect HRQoL, and the perspective of cure after RC or TMT could induce a return to baseline HRQoL values for most of these domains. A considerable amount of data on HRQoL after RC is available, but conflicting results have been reported regarding the effect of urinary diversion (ileal conduit or orthotopic neobladder) and surgical approach (open or robotic surgery) on patient quality of life. Data on HRQoL after TMT are scarce, and additional comparative studies including patients receiving RC (especially using ileal orthotopic neobladder) are needed.	bladder
Actionable genomic landscapes from a real-world cohort of urothelial carcinoma patients.	BACKGROUND: Recent targeted therapies for advanced and metastatic urothelial cancer have generated enthusiasm, but the actionable genomic landscape of early-stage disease remains largely unknown. Here, we utilized a large, real-world cohort to comprehensively investigate the incidence of genetic alterations with potential therapeutic implications at all stages of bladder cancer. MATERIALS AND METHODS: We retrospectively analyzed next-generation sequencing (NGS) data from 1,562 bladder cancer patients (stages I-IV) with formalin-fixed, paraffin-embedded tumor biopsies sequenced using the Tempus xT solid tumor assay. Incidence of genetic alterations, tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 status were assessed and stratified by bladder cancer stage. For patients with tumor-normal match sequencing (n=966), incidental germline alterations in 50 genes were assessed. RESULTS: The cohort was composed of 165 stage I-II, 211 stage III, and 1,186 stage IV tumors. TMB-high, PD-L1 positive, and MSI-high status were noted in 14%, 33%, and 0.7% of tumors, respectively, and were similar across stages. Alterations in fibroblast growth factor receptor (FGFR)2/3, homologous recombination repair genes, additional DNA repair gene mutations (ERCC2, RB1, FANCC), and NTRK fusions were detected at similar frequencies across disease stages. We identified a low rate of incidental germline mutations in all tumors (5.2%) and in specific genes: MUTYH (1.9%), BRCA2 (0.5%), and ATM (0.8%). CONCLUSIONS: Important subsets of patients demonstrate genetic alterations in potentially actionable molecular pathways at all stages. This analysis found minimal variability in these alterations across stages, providing rationale for early identification of genetic alterations and personalization of therapies at all stages for patients with bladder cancer.	bladder
Nomogram to predict overall survival in patients with primary bladder neuroendocrine carcinoma: a population-based study.	Aim: To develop a prognostic model to predict the overall survival of primary bladder neuroendocrine carcinoma (BNEC) patients. Methods: Using univariate and multivariate Cox regression analyses, a nomogram was constructed. Calibration curves, receiver operating characteristic curves and C-index were utilized to evaluate the performance. Results: The study enrolled 906 BNEC patients. The following variables were incorporated in the nomogram: age, marital status, Tumor node metastasis (TNM) stage, chemotherapy and surgery. The nomogram had a C-index of 0.702 in the training cohort and 0.724 in the validation cohort. Conclusion: Compared with the TNM staging system, the proposed nomogram exhibits superior prognostic discrimination and survival prediction.	bladder
GATA3 Expression in Human Tumors: A Tissue Microarray Study on 16,557 Tumors.	INTRODUCTION: GATA3 is a transcription factor involved in epithelial cell differentiation. GATA3 immunostaining is used as a diagnostic marker for breast and urothelial cancer but can also occur in other neoplasms. METHODS: To evaluate GATA3 in normal and tumor tissues, a tissue microarray containing 16,557 samples from 131 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. RESULTS: GATA3 positivity was found in 69 different tumor types including 23 types (18%) with at least one strongly positive tumor. Highest positivity rates occurred in noninvasive papillary urothelial carcinoma (92-99%), lobular carcinoma (98%), carcinoma of no special type of the breast (92%), basal cell carcinoma of the skin (97%), invasive urothelial carcinoma (73%), T-cell lymphoma (23%), adenocarcinoma of the salivary gland (16%), squamous cell carcinoma of the skin (16%), and colorectal neuroendocrine carcinoma (12%). In breast cancer, low GATA3 staining was linked to high pT stage (p = 0.03), high BRE grade (p < 0.0001), HER2 overexpression (p = 0.0085), estrogen and progesterone receptor negativity (p < 0.0001 each), and reduced survival (p = 0.03). CONCLUSION: Our data demonstrate that GATA3 positivity can occur in various tumor entities. Low levels of GATA3 reflect cancer progression and poor patient prognosis in breast cancer.	bladder
Immunohistochemical analysis of expression of VEGFR2, KIT, PDGFR-β, and CDK4 in canine urothelial carcinoma.	Urothelial carcinomas (UCs), also known as transitional cell carcinomas, are the most common canine urinary tract neoplasms. Tyrosine kinases (TKs) are enzymes that tightly regulate cell growth and differentiation through phosphorylation. Receptor TK (RTK) inhibitors are currently used to treat UCs. Toceranib phosphate (Palladia; Pfizer) is an RTK inhibitor that blocks the activity of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor-alpha and -beta (PDGFR-α, -β), FMS-like tyrosine kinase 3, stem cell factor receptor (KIT, kinase inhibitor targeting), and colony stimulating factor receptor. To better understand UCs and validate treatment targets, we performed immunohistochemical staining for RTKs, as well as a novel target, cyclin-dependent kinase 4 (CDK4, a central regulator of the mammalian cell cycle), on formalin-fixed, paraffin-embedded tissues from bladder biopsies from 17 dogs with UCs, 17 dogs with cystitis (diseased controls), and 8 normal dogs (negative controls). Although immunohistochemical scores could not be extrapolated to prognostic value, response to treatment, and outcome of patients with UC, we demonstrated expression of PDGFR-β and VEGFR2 in UCs; all UC samples staining positively for VEGFR2. Minimal positive staining for KIT was noted in the tumor samples. CDK4 staining intensity was significantly weaker in UCs compared with normal and cystitis bladder samples. The intense staining of VEGFR2 in UC cells suggested that VEGFR2 may be of prognostic and/or therapeutic value in dogs with UC. Overexpression of VEGFR2 in UC cells validates this receptor as a treatment target in UC.	bladder
Efficacy and adverse reactions of intra-arterial chemotherapy in patients with bladder cancer: A systematic review and meta-analysis.	This meta-analysis investigated the efficacies of intra-arterial chemotherapy (IAC) plus intravesical chemotherapy (IVC) versus IVC alone in patients with non-muscle-invasive bladder cancer (NMIBC), and preoperative IAC versus preoperative intravenous chemotherapy (IV) in patients with bladder cancer. We also assessed the adverse reactions (ARs) of IAC. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English articles published before April 2021. The qualities of cohort studies and randomized controlled trials were analyzed using the Newcastle-Ottawa Scale and Cochrane risk-of-bias tool, respectively. Effect outcomes were computed by random-effects and fixed-effects models. Statistical analyses were conducted using Stata 16.0 and RevMan v5.3.0. A total of seven articles were included. The analysis revealed that IAC plus IVC significantly prolonged recurrence-free survival (RFS) (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.40-0.76, I(2) = 0%) and progression-free survival (PFS) (HR = 0.59, 95% CI = 0.37-0.97, I(2) = 0%) compared with IVC alone in NMIBC patients after transurethral resection of bladder tumor (TURBT), but had no effect on overall survival (OS), tumor recurrence interval, or tumor-specific death rate. Preoperative IAC had no significant OS benefit compared with preoperative IV in bladder cancer patients. Regarding ARs, patients treated with IAC were significantly more likely to develop grade 1-2 ARs, including nausea/vomiting (odds ratio [OR] = 26.38, 95% CI = 1.88-370.79, I(2) = 78%), neutropenia (OR = 10.15, 95% CI = 3.01-34.24, I(2) = 0%), hypoleukemia (OR = 5.49, 95% CI = 1.38-21.82, I(2) = 26%), and increased alanine aminotransferase (OR = 12.28, 95% CI = 2.24-67.43, I(2) = 0%), but there was no significant difference between grade 1-2 ARs and grade 3-4 ARs in terms of increased creatinine in patients treated with IAC. Therefore, administration of IAC plus IVC after TURBT improved RFS and PFS compared with IAC alone in patients with NMIBC. IAC was associated with mild ARs and was well tolerated by most patients.	bladder
Efficacy of Intravesical Instillation Therapy with Low-Dose Tokyo-172 Bacillus Calmette-Guérin to Prevent Recurrence of Non-Muscle-Invasive Bladder Cancer and Treat Carcinoma in situ: A Multi-Institutional Retrospective Study.	INTRODUCTION: There are various doses, durations, and strains of bacillus Calmette-Guérin (BCG) intravesical instillation therapy, but optimal treatment has not yet been established. We retrospectively investigated the efficacy and safety of low-dose BCG therapy for non-muscle-invasive bladder cancer (NMIBC) and carcinoma in situ (CIS) in a multicenter study. METHODS: From 1991 to 2019, 323 patients who received BCG therapy to prevent recurrence of NMIBC were analyzed as group A. Similarly, 147 patients who received BCG therapy for the treatment of CIS were analyzed as group B. Patients received low- or full-dose Tokyo-172 strain or full-dose Connaught strain, and the three strains were compared. Survival curves were estimated by the Kaplan-Meier method, and independent risk factors for intravesical recurrence were examined by multivariate logistic regression. RESULTS: Recurrence-free survival (RFS) in group A was significantly better for the Connaught strain than the low-dose Tokyo-172 strain (p = 0.026), but not between the low- and full-dose Tokyo-172 strains (p = 0.443). RFS of group B, cancer-specific survival, and progression-free survival in both groups did not show statistically significant differences. Logistic analysis of group A showed that for intravesical recurrence, only pT1 was a significant risk factor, and there were no differences between the BCG strain and dose and no significant factors in group B. There were also no differences in the completion rate in both groups, but adverse events such as urinary frequency and feeling of residual urine were significantly lower with the low-dose Tokyo-172 strain. CONCLUSION: There was no difference in efficacy between the low- and full-dose Tokyo-172 strains, but to minimize adverse events, the low-dose Tokyo-172 strain may be worth considering.	bladder
KDM6A Loss Triggers an Epigenetic Switch That Disrupts Urothelial Differentiation and Drives Cell Proliferation in Bladder Cancer.	Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn repressed FOXA1-target genes and activated cell-cycle progression genes. Importantly, ATF3 depletion reversed the cell proliferation phenotype induced by KDM6A deficiency. These data establish that KDM6A loss engenders an epigenetic state that drives tumor growth in an ATF3-dependent manner, creating a potentially targetable molecular vulnerability. SIGNIFICANCE: A gain-of-function epigenetic switch that disrupts differentiation is triggered by inactivating KDM6A mutations in bladder cancer and can serve as a potential target for novel therapies.	bladder
Long-Term Retention Microbubbles with Three-Layer Structure for Floating Intravesical Instillation Delivery.	Intravesical instillation is an effective treatment for bladder cancer. However, clinical anticancer agents always suffer rapid excretion by periodic urination, leading to low therapeutic efficacy. Prolonging the retention time of drugs in the bladder is the key challenge for intravesical instillation treatment. Herein, a facile and powerful surface cross-linking-freeze drying strategy is proposed to generate ultra-stable albumin bovine air microbubbles (BSA-MBs) that can float and adhere to the bladder wall to overcome the excretion of urination and exhibit a remarkable property of long-term retention in the bladder. More noteworthy, BSA-MBs are endowed with a specific three-layer structure, namely, the outer membrane, middle drug loading layer and inner air core, which makes them have a low density to easily float and possess a high drug loading capacity. Based on their unique superiorities, the therapeutic potential of doxorubicin (DOX)-loaded BSA-MBs (DOX-MBs) is exemplified by intravesical instillation for bladder cancer. After injection into the bladder, DOX-MBs can remain in the bladder for a long time and sustain the release of DOX in urine, exhibiting potent anticancer efficacy. Consequently, the prolonged retention of BSA-MBs in the bladder renders them as an effective floating drug delivery system for intravesical instillation therapy.	bladder